Investigating roles of regulatory T cells in inducing anti-tumur immunity and developing immunotherapy in head and neck cancer

• Project/Area Number: 17K16937
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Nagoya City University
• Principal Investigator: Matoba Takuma 名古屋市立大学, 大学院医学研究科, 臨床研究医 (40790712)
• Research Collaborator: IMAI masaki ; OHKURA naganari ; KAWAKITA daisuke ; IJICHI kei ; TOYAMA tatsuya ; MORITA akimichi ; MURAKAMI shingo ; SAKAGUCHI shimon ; YAMAZAKI sayuri
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 制御性T細胞 / 頭頸部癌 / 抗腫瘍免疫

Outline of Final Research Achievements

Regulatory T cells suppress several types of immunity, including anti-tumor immunity. On the other hand, head and neck cancer, mostly occurred from oral cavity, pharynx and larynx, have been increasing recently. To find out the feature of regulatory T cells in head and neck cancer, we analyzed the phenotypes and gene expression patterns of those cells.
As a result, we found that the frequency of regulatory T cells was increased in head and neck cancer tissue and many of regulatory T cells expressed immune-suppressive molecules. Furthermore, we found the signature gene expression patterns of those regulatory T cells.

Academic Significance and Societal Importance of the Research Achievements

近年、免疫チェックポイント阻害薬をはじめ、癌に対する免疫が注目されている。しかし、そのメカニズムはまだ明らかになっていない部分も多い。頭頸部癌に対しても免疫チェックポイント阻害薬が使用可能となったが、効果の不十分な場合も多く、メカニズムの解明が求められている。
私たちは抗腫瘍免疫を抑える制御性T細胞が、頭頸部癌においてどのような特徴をもつかを見出した。発現する分子や遺伝子などのデータを生かし、頭頸部癌に対する免疫治療のよい適応や他の治療法との組み合わせなどを決定することに役立たせることができる。

Research Products

• [Journal Article] Regulatory T cells expressing abundant CTLA-4 on the cell surface with a proliferative gene profile are key features of human head and neck cancer. (2019)
  • Author(s): Matoba T, Imai M, Ohkura N, Kawakita D, Ijichi K, Toyama T, Morita A, Murakami S, Sakaguchi S, Yamazaki S.
  • Journal Title: International Journal of Cancer Volume: 144(11) Issue: 11 Pages: 2811-2822
  • DOI: 10.1002/ijc.32024
  • Peer Reviewed / Open Access
• [Presentation] 頭頸部癌における制御性T細胞の新たな特徴 (2019)
  • Author(s): 的場拓磨、今井優樹、大倉永也、川北大介、伊地知圭、遠山竜也、森田明理、村上信五、坂口志文、山崎小百合
  • Organizer: 第37回日本耳鼻咽喉科免疫アレルギー学会
• [Presentation] A new feature of regulatory T cells in human head and neck cancer (2018)
  • Author(s): Takuma Matoba, Masaki Imai, Naganari Ohkura, Daisuke Kawakita, Kei Ijichi, Tatsuya Toyama, Akimichi Morita, Shingo Murakami, Shimon Sakaguchi, Sayuri Yamazaki
  • Organizer: 第47回日本免疫学会学術集会
  • Int'l Joint Research